The ability to sequence deoxyribonucleic acid (DNA) accurately and rapidly is revolutionizing biology and medicine. The pharmacogenomics challenge is to comprehensively identify the genes and functional polymorphisms associated with the variability in drug response. Screens for numerous genetic markers performed for populations large enough to yield statistically significant data are needed before associations can be made between a given genotype and a particular disease.
The study of complex genomes, and in particular, the search for the genetic basis of disease in humans, requires genotyping on a massive scale, which is demanding in terms of cost, time, and labor. Such costly demands are even greater when the methodology employed involves serial analysis of individual DNA samples, i.e., separate reactions for individual samples. Resequencing of polymorphic areas in the genome that are linked to disease development will contribute greatly to the understanding of diseases, such as cancer, and therapeutic development. Oligonucleotide libraries are the cornerstone of sequence-based gene resequencing and digital profiling strategies. To realize the full commercial potential of various high-throughput sequencing platforms, the cost of generating oligonucleotide libraries must be reduced by a substantial amount. Thus, there is a need for cost-effective methods for preparing populations of high quality oligonucleotide probes with sufficient yield for use in high throughput sequencing platforms and solution based capture methods.